Sodium hydride → 3'-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-2',3',4',5'-tetrahydro-1H-[2,4']biimidazolyl-1'-carboxylic acid tert-butyl ester

HRID 417471Notes

Reaction equation

HRID 417471 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][CH:13]([C:15]2[NH:16][CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]#[C:27][C:28]4[CH:33]=[CH:32][C:31]([C:34]5[N:35]=[C:36]([CH:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:54])[CH:45]([NH:49][C:50]([O:52][CH3:53])=[O:51])[CH:46]([CH3:48])[CH3:47])[NH:37][CH:38]=5)=[CH:30][CH:29]=4)=[CH:22][CH:21]=3)[N:19]=2)[N:12]([C:55](=[O:65])[CH:56]([NH:60][C:61]([O:63][CH3:64])=[O:62])[CH:57]([CH3:59])[CH3:58])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:66][Si:67]([CH3:74])([CH3:73])[CH2:68][CH2:69][O:70][CH2:71]Cl>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[CH2:14][CH:13]([C:15]2[N:16]([CH2:71][O:70][CH2:69][CH2:68][Si:67]([CH3:74])([CH3:73])[CH3:66])[CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]#[C:27][C:28]4[CH:33]=[CH:32][C:31]([C:34]5[N:35]=[C:36]([CH:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:54])[CH:45]([NH:49][C:50]([O:52][CH3:53])=[O:51])[CH:46]([CH3:48])[CH3:47])[N:37]([CH2:71][O:70][CH2:69][CH2:68][Si:67]([CH3:74])([CH3:73])[CH3:66])[CH:38]=5)=[CH:30][CH:29]=4)=[CH:22][CH:21]=3)[N:19]=2)[N:12]([C:55](=[O:65])[CH:56]([NH:60][C:61]([O:63][CH3:64])=[O:62])[CH:57]([CH3:58])[CH3:59])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178502176HCID 178502176, compound

Product 1

HCID 866488803'-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-2',3',4',5'-tetrahydro-1H-[2,4']biimidazolyl-1'-carboxylic acid tert-butyl esterYield 156.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in mineral oil, 27 mg, 0.55 mmol) was added to a solution of 3′-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-2′,3′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-1′-carboxylic acid tert-butyl ester (248 mg, 0.23 mmol) in dimethylformamide (8 mL) under an atmosphere of nitrogen at 0° C. After 15 minutes 2-(trimethylsilyl)ethoxymethyl chloride (107.5 μL, 0.48 mmol) was added and the reaction was allowed to warm to ambient temperature. After 2 hours the solvent was removed under reduced pressure. The residue was taken up in dichloromethane (50 mL) washed with water (20 mL), and dried over sodium sulfate and filtered. The solvent was removed under reduced pressure. The residue was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to yield 3′-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-2′,3′,4′,5′-tetrahydro-1H-[2,4]biimidazolyl-1′-carboxylic acid tert-butyl ester (410 mg, 0.36 mmol). C58H85N9O10Si2 calculated 1123.6 observed [M+1]+1124.7; rt=3.10 min.

Workup

  1. customAfter 2 hours the solvent was removed under reduced pressure
  2. washwashed with water (20 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-3a5b1c9d5d874bab9e834af0e1d28ed2
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Reaction notes

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